Stem cells (SCs) are the core research area of our Team. We conduct projects that are related to the SCs on different levels, starting from the cell biology, through functional aspects and finally innovative approaches of SC utilization in tissue regeneration. SCs are the unique type of cells, that possess capacity to self-renew and differentiate into different types of cells. They might be classified according to their differentiation potency, developmental level (embryonic vs. somatic) or tissue origin. 

In our studies we mainly work on mesenchymal stem/stromal cells (MSCs), induced pluripotent SCs (iPSCs), as well as hematopoietic SCs (HSCs). 

Our mission is not only to elucidate the molecular mechanisms responsible for the functional properties of different SC populations and their derivatives, but most importantly to utilize them for the purposes of the biomedical science, with special focus on the regenerative medicine. Particularly, we attempt to develop innovative approaches of SC use as therapeutic agents in the treatment of cardiovascular diseases, orthopedics and hematology. 

Mesenchymal stem/stromal cells (MSCs) are multipotent SCs typically isolated from bone marrow, adipose tissue, or umbilical cord. They are defined as adherent cells expressing mesenchymal markers (e.g. CD90, CD73, CD105), with concomitant absence of hematopoietic antigens (e.g. CD45, CD34, CD16, CD19, HLA-DR). They possess ability to differentiate into mesodermal lineages (bone, cartilage, fat) and exert strong paracrine, as well as immunomodulatory properties. 

Following current directions in the field of tissue regeneration, apart from working on primary MSCs of various tissue origin, we also conduct our research on immortalized MSCs line. 

Our team actively investigates the pro-regenerative capacities of EVs isolated from native, as well as genetically modified MSCs, in terms of their pro-angiogenic, anti-fibrotic or cytoprotective impact on ischemic tissues. 

Induced pluripotent stem cells (iPSCs) originate from the somatic cells that were reprogrammed with the use of pluripotency-related factors (e.g. OCT4/SOX2/KLF4/c-MYC) to a pluripotent state, which makes them capable of differentiating into any adult cell type. iPSCs were initially created in 2006 by the group of prof. Yamanaka, who was awarded for this work with the Nobel Prize in 2012. 

We possess our own human and murine iPS cell lines obtained by viral transfection, however we also work on the commercially available human iPSCs. They serve as donor cells for the EV-related studies, as well as a source of iPS-derived model cell lines including endothelium (iECs), cardiac fibroblasts (iCFs) and cardiomyocytes (iCMs), that we have established in our laboratory by the optimization of differentiation protocols. 

Hematopoietic stem cells (HSCs) are self-renewing SCs that generate all blood lineages. They are primarily found in bone marrow (BM), but also in mobilized peripheral blood (MPB) and cord blood (CB). HSCs are the therapeutic backbone of hematopoietic stem cell transplantation for leukemias, lymphomas, marrow failure, and some inherited disorders.  

In our studies we specifically concentrate on CB-derived HSCs (CB-HSCs), as their application has become a desirable approach alternative to BM or MPB transplantation in patients with various types of hematological disorders. However, despite the effective use of CB in pediatric patients, its use in adults is still limited by the restricted volume of CB collected during a labor, which may lead to the insufficient number of transplanted HSCs.  

Thus, in our studies  attempt to develop new EV-based strategies that would improve the biological potential of CB-HSCs and subsequently their therapeutic success in adult patients. Indeed, we have demonstrated that EVs secreted by human iPSCs (hiPSC-EVs) enhance several biological properties of CB-HSCs in vitro and in vivo, leading to the enhancement of their ability to reconstitute the hematopoietic system following transplantation. 

These results may have not only a cognitive, but also a practical importance, constituting the basis for the development of innovative solutions aimed at increasing functional potential of CB-HSCs ex vivo prior to their transplantation. Thus, these studies are in line with current global trends related to attempts to increase the possibilities of using CB in the hematology.

Since several years our Team has intensively been conducting research on extracellular vesicles (EVs), with special focus on EVs secreted by different SC populations. 

Extracellular vesicles (EVs) are heterogenous group of submicron membrane-enclosed vesicles released by various types of cells. Their presence has been demonstrated in several body fluids, including saliva, urine, milk or amniotic fluid. Initially, EV classification was based on their size range and the cellular compartment of their origin, recognizing three groups of EVs: exosomes, ectosomes and apoptotic bodies. 

Exosomes are a group of vesicles ranging in size from 30 nm to 120 nm. They are secreted by exocytosis as a result of the fusion of multivesicular bodies (MVBs) with the cell membrane. Exosomes are considered to be enriched in several proteins such as tetraspanins (CD9, CD63, CD81), heat shock family, as well as Alix or TSG100. Ectosomes (microvesicles), have a diameter of 50 nm to 1 μm and are released from the cell surface by the cell membrane protrusion and vesicle budding. They are enriched in selectins, integrins,  phosphatidylserine and other cell-membrane molecules characteristic for their parental cells. 

Apoptotic bodies are bigger vesicles (50 nm to 2 μm) formed as a result of cell fragmentation during the process of apoptosis, shown to be enriched in histones and phosphatidylserine and DNA fragments. 

There has been a mounting evidence that EVs may harbor bioactive cargo in the form of proteins, lipids, mRNA, miRNA, and other regulatory factors. What is more, growing number of scientific reports, including ours, has confirmed that EVs play an important role in the paracrine activity of cells, participating in the horizontal transfer of bioactive molecules that might be delivered into the target cells.  

Importantly, EVs secreted by SCs are of special focus in the field of tissue regeneration and thus in our area of interest. We not only explore their functional activity and influence on several types of target cells, but also we attempt to reveal the molecular mechanisms responsible for their pro-regenerative and immunomodulatory properties, with special focus on the role of miRNA. 

The use of biomaterials as supportive factors for SCs and SC-EVs is also our area of interest. We collaborate with several leading polish institutions specializing in the field of design, synthesis and modification of biocompatible materials, in order to develop innovative approaches of tissue engineering.  

We attempt to utilize several types of biomaterials, including graphene and its derivatives, polyurethanes, hydrogels and composites, as substrates or scaffolds for SCs culture or delivery, respectively. Additionally, together with Faculty of Chemistry JU we have also developed an innovative method of EV cryopreservation, that relies on the use of polyelectrolytes.